Read by QxMD icon Read


E Y Scott, M C T Penedo, J D Murray, C J Finno
Equine cerebellar abiotrophy (CA) is a hereditary neurodegenerative disease that affects the Purkinje neurons of the cerebellum and causes ataxia in Arabian foals. Signs of CA are typically first recognized either at birth to any time up to 6 months of age. CA is inherited as an autosomal recessive trait and is associated with a single nucleotide polymorphism (SNP) on equine chromosome 2 (13074277G>A), located in the fourth exon of TOE1 and in proximity to MUTYH on the antisense strand. We hypothesize that unraveling the functional consequences of the CA SNP using RNA-seq will elucidate the molecular pathways underlying the CA phenotype...
October 5, 2016: Cerebellum
Monica Marabelli, Valeria Molinaro, Raefa Abou Khouzam, Enrico Berrino, Mara Panero, Antonella Balsamo, Tiziana Venesio, Guglielmina Nadia Ranzani
AIMS: Colorectal adenomatous polyposis entailing cancer predisposition is caused by constitutional mutations in different genes. APC is associated with the familial adenomatous polyposis (FAP/AFAP) and MUTYH with the MUTYH-associated polyposis (MAP), while POLE and POLD1 mutations cause the polymerase proofreading-associated polyposis (PPAP). METHODS: We screened for mutations in patients with multiple adenomas/FAP: 121 patients were analyzed for APC and MUTYH mutations, and 36 patients were also evaluated for POLE and POLD1 gene mutations...
October 5, 2016: Genetic Testing and Molecular Biomarkers
Takahide Hayano, Hiroshi Matsui, Hirofumi Nakaoka, Nobuaki Ohtake, Kazuyoshi Hosomichi, Kazuhiro Suzuki, Ituro Inoue
Prostate cancer (PC) is the second most common cancer in men. Family history is the major risk factor for PC. Only two susceptibility genes were identified in PC, BRCA2 and HOXB13. A comprehensive search of germline variants for patients with PC has not been reported in Japanese families. In this study, we conducted exome sequencing followed by Sanger sequencing to explore responsible germline variants in 140 Japanese patients with PC from 66 families. In addition to known susceptibility genes, BRCA2 and HOXB13, we identified TRRAP variants in a mutually exclusive manner in seven large PC families (three or four patients per family)...
2016: PloS One
Shunji Nakatake, Yusuke Murakami, Yasuhiro Ikeda, Noriko Morioka, Takashi Tachibana, Kohta Fujiwara, Noriko Yoshida, Shoji Notomi, Toshio Hisatomi, Shigeo Yoshida, Tatsuro Ishibashi, Yusaku Nakabeppu, Koh-Hei Sonoda
Oxidative stress is implicated in various neurodegenerative disorders, including retinitis pigmentosa (RP), an inherited disease that causes blindness. The biological and cellular mechanisms by which oxidative stress mediates neuronal cell death are largely unknown. In a mouse model of RP (rd10 mice), we show that oxidative DNA damage activates microglia through MutY homolog-mediated (MUYTH-mediated) base excision repair (BER), thereby exacerbating retinal inflammation and degeneration. In the early stage of retinal degeneration, oxidative DNA damage accumulated in the microglia and caused single-strand breaks (SSBs) and poly(ADP-ribose) polymerase activation...
September 22, 2016: JCI Insight
Afaf Elsaid, Rami Elshazli, Fatma El-Tarapely, Hossam Darwish, Camelia Abdel-Malak
Colorectal cancer (CRC) is a heterogeneous triat that involves both environmental and genetic factors. Genetic mutations of MUTYH (p.Y179C and p.G396D) have been reported to be associated with increased risk of CRC among several ethnic populations. The aim of this work is to assess the association of the monoallelic MUTYH mutations (p.Y179C and p.G396D) with increased risk of CRC among Egyptian patients. This study included 120 unrelated CRC Egyptian patients who were compared with 100 healthy controls from the same locality...
September 8, 2016: Familial Cancer
Maya Kappil, Mary Beth Terry, Lissette Delgado-Cruzata, Yuyan Liao, Regina M Santella
BACKGROUND: Major breast cancer susceptibility genes involved in DNA repair, including BRCA1 and BRCA2, have been identified. However, mutations in these genes account for only 5-10% of identified breast cancer cases. Additional DNA repair pathway genes may also contribute to susceptibility. MATERIALS AND METHODS: We investigated the association between 12 single nucleotide polymorphisms (SNPs) in mismatch repair (MMR) genes and breast cancer risk among 313 sister-sets enrolled in the New York site of the Breast Cancer Family Registry (BCFR) (n=744) using conditional logistic regression analysis...
September 2016: Anticancer Research
María Arriba, Ricardo Sánchez, Daniel Rueda, Laura Gómez, Juan L García, Yolanda Rodríguez, José Antonio Pajares, Jessica Pérez, Miguel Urioste, Rogelio González Sarmiento, José Perea
BACKGROUND: Two or more primary colorectal tumors coexisting at the time of diagnosis are considered to be synchronous tumors. It is estimated that synchronous colorectal cancer (SCRC) only accounts for 1.1% to 8.1% of all colorectal cancers (CRCs), and its molecular basis is still poorly understood. PATIENTS AND METHODS: We evaluated the microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP) statuses in a series of 49 patients (98 tumors) diagnosed with sporadic SCRC at the 12 de Octubre University Hospital with the aim of improving the molecular characterization of this type of tumor...
August 9, 2016: Clinical Colorectal Cancer
Jineun Kim, Seoyun Yum, Changwon Kang, Suk-Jo Kang
Cancer arises from complex, multi-layer interactions between diverse genetic and environmental factors. Genetic studies have identified multiple loci associated with tumor susceptibility. However, little is known about how germline polymorphisms interact with one another and with somatic mutations within a tumor to mediate acquisition of cancer traits. Here, we survey recent studies showing gene-gene interactions, also known as epistases, affecting genetic susceptibility in colorectal, gastric and esophageal cancers...
August 30, 2016: Oncotarget
Matthew J Burak, Kip E Guja, Elena Hambardjieva, Burak Derkunt, Miguel Garcia-Diaz
8-oxo-7,8-dihydroxy-2'-deoxyguanosine (8-oxo-dG) has high mutagenic potential as it is prone to mispair with deoxyadenine (dA). In order to maintain genomic integrity, post-replicative 8-oxo-dG:dA mispairs are removed through DNA polymerase lambda (Pol λ)-dependent MUTYH-initiated base excision repair (BER). Here, we describe seven novel crystal structures and kinetic data that fully characterize 8-oxo-dG bypass by Pol λ. We demonstrate that Pol λ has a flexible active site that can tolerate 8-oxo-dG in either the anti- or syn-conformation...
September 15, 2016: EMBO Journal
Ronja Adam, Isabel Spier, Bixiao Zhao, Michael Kloth, Jonathan Marquez, Inga Hinrichsen, Jutta Kirfel, Aylar Tafazzoli, Sukanya Horpaopan, Siegfried Uhlhaas, Dietlinde Stienen, Nicolaus Friedrichs, Janine Altmüller, Andreas Laner, Stefanie Holzapfel, Sophia Peters, Katrin Kayser, Holger Thiele, Elke Holinski-Feder, Giancarlo Marra, Glen Kristiansen, Markus M Nöthen, Reinhard Büttner, Gabriela Möslein, Regina C Betz, Angela Brieger, Richard P Lifton, Stefan Aretz
In ∼30% of families affected by colorectal adenomatous polyposis, no germline mutations have been identified in the previously implicated genes APC, MUTYH, POLE, POLD1, and NTHL1, although a hereditary etiology is likely. To uncover further genes with high-penetrance causative mutations, we performed exome sequencing of leukocyte DNA from 102 unrelated individuals with unexplained adenomatous polyposis. We identified two unrelated individuals with differing compound-heterozygous loss-of-function (LoF) germline mutations in the mismatch-repair gene MSH3...
August 4, 2016: American Journal of Human Genetics
Maya A Kappil, Yuyan Liao, Mary Beth Terry, Regina M Santella
AIM: The expression level of DNA repair-related genes and their association with breast cancer status among participants of the New York site of the Breast Cancer Family Registry was investigated. MATERIALS AND METHODS: RNA from mononuclear cells in 194 sister sets (n=475 women) were assayed for ATM, BRCA1, MSH2, MUTYH and XPC gene expression levels and analyzed using generalized estimating equations (GEE). RESULTS: Individuals with decreased ATM and MSH2 expression had significantly higher odds for breast cancer compared to individuals with higher levels of expression (odds ratio (OR)=1...
August 2016: Anticancer Research
Hiroyuki Kamiya, Masahiro Kurokawa, Tetsuaki Makino, Miwako Kobayashi, Ichiro Matsuoka
INTRODUCTION: In DNA, 8-oxo-7,8-dihydroguanine (G(O), 8-hydroxyguanine) is one of the most pivotal oxidatively damaged bases and induces G:C → T:A transversion mutations. DNA polymerase λ preferentially inserts dCTP opposite G(O) in vitro, and this error-free bypass function is considered to be important after A base removal from G(O):A pairs by the MUTYH DNA glycosylase. To examine the effects of reduced levels of DNA polymerase λ on the G(O)-induced mutations, the polymerase was knocked-down in human U2OS cells, and a shuttle plasmid DNA containing a G(O):C pair at position 122 in the supF gene was transfected into the cells...
2015: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
Jun Yang, Wei Qing Liu, Wen Liang Li, Cheng Chen, Zhu Zhu, Min Hong, Zhi Qiang Wang, Jian Dong
The aim of this study was to investigate germline mutations of the APC, MUTYH and AXIN2 genes in Chinese patients with familial adenomatous polyposis (FAP), and further assess the value of bioinformatics in screening the pathogenic changes predisposing to FAP. APC genes from 11 unrelated FAP patients in Yunnan province in China were firstly examined by exon-specific DNA sequencing. For samples without already known pathogenic changes predisposing to FAP in the APC gene, whole-gene sequencing of MUTYH and AXIN2 was performed...
July 2016: Oncology Letters
Gabriela Möslein
Due to the advances in molecular genetic diagnostics of adenomatous polyposis variants, identification of patients with a genetic predisposition and their at risk relatives is becoming increasingly important in clinical practice. Precise knowledge of the specific risk profile is gaining significance especially for surgeons and requires a clinically differentiated approach in order to correctly identify the indications for prophylactic surgery. In this article reference will be made to the technical details of the pouch operation rather than the decision-making process per se, since this has become common knowledge for specialized colorectal surgeons...
August 2016: Der Chirurg; Zeitschrift Für Alle Gebiete der Operativen Medizen
Piotr Czarny, Dominik Kwiatkowski, Monika Toma, Joanna Kubiak, Agnieszka Sliwinska, Monika Talarowska, Janusz Szemraj, Michael Maes, Piotr Galecki, Tomasz Sliwinski
Elevated level of DNA damage was observed in patients with depression. Furthermore, single nucleotide polymorphisms (SNPs) of base excision repair (BER) genes may modulate the risk of this disease. Therefore, the aim of this study was to delineate the association between DNA damage, DNA repair, the presence of polymorphic variants of BER genes, and occurrence of depression. The study was conducted on peripheral blood mononuclear cells of 43 patients diagnosed with depression and 59 controls without mental disorders...
June 21, 2016: Molecular Neurobiology
Gene M Weinstein, Knarik Arkun, James Kryzanski, Michael Lanfranchi, Gaurav K Gupta, Harprit Bedi
Ependymomas are common spinal lesions, with the vast majority arising in an intramedullary location. Several cases have been described in the literature of ependymomas in an intradural, extramedullary location. The authors present a case of a 56-year-old female who presented with several weeks of lower back pain and weakness. MRI revealed an intradural, extramedullary enhancing mass at L1-L2. The mass was successfully resected surgically. Pathologic evaluation revealed a low grade glioma with components of both ependymoma and pilocytic astrocytoma with MUTYH G382D mutation...
2016: Case Reports in Pathology
Andrea R Cajal, Tamara A Piñero, Alicia Verzura, Juan Pablo Santino, Angela R Solano, Pablo G Kalfayan, Alejandra Ferro, Carlos Vaccaro
Lynch syndrome is the most frequent syndrome in hereditary colorectal cancer, a family-specific deleterious mutations in genes encoding DNA reparation proteins: MLH1 (mutL homolog 1), MSH2, MSH6 (mutS homolog 2 y 6, respectively), PMS2 (PMS1 homolog 2, mismatch repair system component) y MUTYH (mutY DNA glycosylase). The c.2252_2253delAA, p.Lys751Serfs*3 mutation in MLH1 gene segregates with a haplotype reported in the northern region of Italy and whose origin was attributed to a founder effect. This mutation co-segregates with typical characteristics of Lynch syndrome, including early age at onset and multiple primary tumors in the same individual, a high frequency of pancreatic cancer, high microsatellite instability and lack of PMS2 expression...
2016: Medicina
Kazuya Shinmura, Hisami Kato, Yuichi Kawanishi, Kimio Yoshimura, Hisaki Igarashi, Masanori Goto, Hong Tao, Yusuke Inoue, Takayuki Sugiyama, Hiroshi Furuse, Seiichiro Ozono, Haruhiko Sugimura
8-Hydroxyguanine (8OHG), a major oxidative DNA lesion, is known to accumulate in prostate cancer; however, the status of one of its repair enzymes, MUTYH, in prostate cancer remains to be elucidated. In this study, we showed that the expression levels of MUTYH mRNA and protein were significantly lower in prostate cancer than in non-cancerous prostatic tissue by examining two independent, publicly available databases and by performing an immunohistochemical analysis of prostate cancer specimens obtained at our hospital, respectively...
June 2, 2016: Molecular Carcinogenesis
Nona Abolhassani, Julio Leon, Zijing Sheng, Sugako Oka, Hideomi Hamasaki, Toru Iwaki, Yusaku Nakabeppu
In normal brain, neurons in the cortex and hippocampus produce insulin, which modulates glucose metabolism and cognitive functions. It has been shown that insulin resistance impairs glucose metabolism and mitochondrial function, thus increasing production of reactive oxygen species. Recent progress in Alzheimer's disease (AD) research revealed that insulin production and signaling are severely impaired in AD brain, thereby resulting in mitochondrial dysfunction and increased oxidative stress. Among possible oxidative DNA lesions, 8-oxoguanine (8-oxoG) is highly accumulated in the brain of AD patients...
May 24, 2016: Mechanisms of Ageing and Development
Aung Ko Win, Jeanette C Reece, James G Dowty, Daniel D Buchanan, Mark Clendenning, Christophe Rosty, Melissa C Southey, Joanne P Young, Sean P Cleary, Hyeja Kim, Michelle Cotterchio, Finlay A Macrae, Katherine M Tucker, John A Baron, Terrilea Burnett, Loïc Le Marchand, Graham Casey, Robert W Haile, Polly A Newcomb, Stephen N Thibodeau, John L Hopper, Steven Gallinger, Ingrid M Winship, Noralane M Lindor, Mark A Jenkins
Germline mutations in the DNA base excision repair gene MUTYH are known to increase a carrier's risk of colorectal cancer. However, the risks of other (extracolonic) cancers for MUTYH mutation carriers are not well defined. We identified 266 probands (91% Caucasians) with a MUTYH mutation (41 biallelic and 225 monoallelic) from the Colon Cancer Family Registry. Mutation status, sex, age and histories of cancer from their 1,903 first- and 3,255 second-degree relatives were analyzed using modified segregation analysis conditioned on the ascertainment criteria...
October 1, 2016: International Journal of Cancer. Journal International du Cancer
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"